Approximately 20-25 percent of the world's babies have iron-deficiency anemia, and a much higher proportion has iron deficiency without anemia. The proposed 5-year project uses a brain/behavior framework to determine long-term effects of this common problem. The project's Specific Aims are to 1) establish whether neurophysiologic changes in iron-deficient anemic infants represent irregular progressions or arrests in neuromaturation; 2) identify long-term effects of preventing iron deficiency in infancy; 3) determine the effects of timing of iron-deficiency anemia in infancy on long-term outcome; and 4) characterize family/environmental factors that exacerbate or ameliorate poorer outcome. The project will reassess 1200 Chilean 10-year-olds who participated in NIH-supported studies as infants and preschoolers. Follow-up measures are based on new research on iron's role in the developing brain (effects on myelination, dopaminergic neurotransmission, and neuronal metabolism). A neuromaturation component uses advanced methods to assess sensory systems (ABRs, VEPs), spontaneous motor activity, sleep-wake cycle and autonomic nervous system, neurocognitive functions (with ERP), and neuroendocrine responses. The measures pursue findings of alterations in infancy and/or at 3-5 years. This component will involve 50 children who had iron-deficiency anemia at 6 months, 80 identified at 12 months. and 20 identified at 18 months; 50 children who were nonanemic at 6 months and received iron for a year will serve as the control group. The other component will determine the long-term effects of preventing iron deficiency in infancy. Evaluation of all 1200 children will pursue our findings of effects of iron supplementation on motor milestones, information processing. and behavior. The overall design supports analysis of outcome by age of iron-deficiency anemia to identify functions that are more or less affected, depending on developmental stage. and takes a comprehensive approach to environmental risk. The project promises to be a major advance in understanding this common nutrient deficiency and will inform policy decisions regarding the prevention and treatment of early iron deficiency in industrialized and developing countries alike.